100 years of insulin: celebrating the past, present and future of diabetes therapy

Abstract

The year 2021 marks the centennial of Banting and Best's landmark description of the discovery of insulin. This discovery and insulin's rapid clinical deployment effectively transformed type 1 diabetes from a fatal diagnosis into a medically manageable chronic condition. In this Review, we describe key accomplishments leading to and building on this momentous occasion in medical history, including advancements in our understanding of the role of insulin in diabetes pathophysiology, the molecular characterization of insulin and the clinical use of insulin. Achievements are also viewed through the lens of patients impacted by insulin therapy and the evolution of insulin pharmacokinetics and delivery over the past 100 years. Finally, we reflect on the future of insulin therapy and diabetes treatment, as well as challenges to be addressed moving forward, so that the full potential of this transformative discovery may be realized.

Fig. 1 |. A timeline of key discoveries in our understanding of insulin and diabetes pathophysiology.

Shown in the main branch of the timeline are key discoveries in our understanding of insulin as a central contributor to diabetes pathophysiology^{,,,–,–,,,}. Included in the left branch of the timeline are important milestones that have enabled the understanding of type 2 diabetes as a disease of impaired insulin secretion and action^{,,–,,,,–,,–}. The right branch highlights notable discoveries that have led to the understanding of type 1 diabetes as an autoimmune disease^{,,–,–,–,–,–,,,–}.

Fig. 2 |. The evolution of improvements in insulin pharmacokinetics.

a, The native structure of human proinsulin. b, Representative pharmacokinetic profiles of available insulins administered subcutaneously. c, Structural changes of insulin analogs and years of introduction in the USA including rapid-acting insulin analogs (green boxes) and long-acting insulin analogs (red boxes)^,,–.

Fig. 3 |. Advances in diabetes management viewed through the lens of individuals with type 1 diabetes.

The full names of contributing individuals for the years 1965–2006 are included in the Acknowledgements. The quotes from K.R. (diagnosed 1929) and G.P. (diagnosed 1934) are from ref. . The quote from J.W. (diagnosed 1948) is from ref. . The quote from C.C. (diagnosed 1955) is from ref. .

Fig. 4 |. The future of insulin and diabetes therapy.

The future of diabetes therapy and prevention includes efforts focused on: the development of a renewable, cellular source of insulin; improvements in technology, including better insulins and novel insulin delivery platforms; and disease-modifying therapies, including immune-modulating therapies and beta cell supportive agents. Quotes are included from individuals who depend on insulin, expressing their hopes surrounding the future of diabetes therapy. Image originally created using biorender.com and AutoDesk SketchBook.